Oxacillin-resistant Staphylococcus aureus isolates have been detected with increasing frequency in NIH Clinical Center patients. Such isolates have the potential for becoming serious epidemiological and treatment problems. This review will examine the spectrum of oxacillin resistance found in these isolates, the frequency and degree of resistance to other antimicrobial agents, and the usefulness of bacteriophage typing in distinguishing among the different isolates. Useful procedures for detecting the oxacillin resistance of these isolates in the clinical laboratory will be investigated.